Skin is an important tissue for separating a living body and an outside world. Accordingly, if the skin suffers disorder, it means that the protective barrier of the living body collapses, and the disorder may cause serious damage to the living body. In this context, disorders such as damage on the skin need to be eliminated rapidly. However, a protective barrier function of the skin becomes a hindrance for allowing a drug for eliminating the disorder to reach the skin, especially to the dermis, and hence there was a condition that smooth elimination of the disorder hardly occurs. Accordingly, there is a need to develop a technique to accurately deliver a drug to be delivered to the dermis.
Under the above-mentioned condition as a background, there have been attempted various developments on means for promoting percutaneous absorption. For example, there are exemplified: a method involving utilizing a card-house or net-work structure formed by an oil-based gel (Patent Document 1); a method involving utilizing an ultrasonic wave as a driving force for percutaneous absorption (Patent Document 2); a method involving utilizing a solvent such as N-methyl-2-pyrrolidone (Patent Document 3); a method involving utilizing a percutaneous absorption promoting ingredient such as lauroyl sarcosine (Patent Document 4); and a method involving allowing a liposome or a niosome, which is a sphere having a phospholipid bilayer structure including an aqueous core, to encapsulate a drug into the aqueous core and blending the resultant to an external preparation for skin (Patent Document 5). Those technologies enabled improvements in reaching degree of a drug to the dermis, but the reaching degree was far from sufficient, and in considerable cases, the above-mentioned means for promoting percutaneous absorption impaired the defense function of the skin itself.
On the other hand, as a formulation technique utilizing a vesicle, there are known techniques in which insoluble ingredients such as a ceramide and phytosterol are stably blended in an external preparation for skin (Patent Document 6 and Patent Document 7). Further, there is also known a technique in which an ingredient that is reactive with water is encapsulated into a vesicle to stably contain the vesicle into a water-based formulation (Patent Document 8). However, in those vesicle techniques, a surfactant for forming the vesicle is a cationic surfactant. Accordingly, its application other than to washing material is difficult, and there were many cases in which the stability of the vesicle itself was problematic. As a result, it is difficult to apply the vesicle to an external preparation for skin which is not capable of being washed off.
On the other hand, a vesicle, which contains an α,ε-bis (ε-N—(C10-30)acylglutamyl)lysine and/or a salt thereof, is completely unknown.
It should be noted that, an extract of Coptis (Ranunculaceae), an extract of Citrus aurantium (Rutaceae), an extract of red algae, and an extract of Houttuynia (Saururaceae) each have a function of adjusting the calcium ion concentration gradient of the epidermis to reinforce the skin barrier function (Patent Document 9). It is known that an extract of Rosmarinus officinalis has a function of suppressing decomposition of elastin (Patent Document 10). It is known that an extract of Betula alba has a function of suppressing a Maillard reaction (Patent Document 11). It is known that extracts of Achillea and Ophiopogon each have a function of suppressing extension of dendrite in melanocyte (Patent Document 12 and Patent Document 13). It is known that an extract of Syzygium aromaticum, and triterpenes such as oleanolic acid, betulinic acid, and betuline each have a function to restore dermis collagen fiber bundle (Patent Document 14 and Patent Document 15). It is known that a natural protein hydrolysate has a function to inhibit elastase (Patent Document 16). It is known that pantetheine sulfonate or a derivative thereof and glycyrrhetinic acid or a derivative thereof each have a function of suppressing an inflammatory factor. It is known that hydroquinone or a glycoside thereof, esculin, esculetin, glabridin, methoxysalicylic acid, tranexamic acid or a derivative thereof, and ascorbic acid or a derivative thereof each have a function of eliminating active oxygen to prevent oxidation stress from being applied onto the dermis (Patent Document 17).    [Patent Document 1] JP 2000-103722 A    [Patent Document 2] JP H11-335271 A    [Patent Document 3] JP H10-265379 A    [Patent Document 4] JP H09-169637 A    [Patent Document 5] JP 2004-143080 A    [Patent Document 6] JP 2006-199635 A    [Patent Document 7] JP 2006-199634 A    [Patent Document 8] JP H09-40543 A    [Patent Document 9] JP 2006-331294 A    [Patent Document 10] JP 2005-132823 A    [Patent Document 11] JP 2005-35911 A    [Patent Document 12] JP 2003-113027 A    [Patent Document 13] JP 2004-250354 A    [Patent Document 14] JP 2002-29988 A    [Patent Document 15] JP H09-143050 A    [Patent Document 16] JP 2004-182687 A    [Patent Document 17] JP 2000-344653 A